Our work has shown that polysomal messenger RNA populations of regenerating and pre-neoplastic rat liver differ only quantitatively from those of normal livers. Qualitative changes, if present, are likely to be limited to the expression of a small set of genes. Experiments are in progress to determine if the main alteration in polysomal mRNA of primary hepatomas, induced in rats by feeding a choline-deficient diet containing 0.05% ethionine, also consists of shifts in the frequency of polysomal mRNAs which exist in normal livers. Furthermore, we will determine if the abundance of the mRNA coding for a protein which is similar to the transforming protein of avian sarcoma viruses, changes during liver regeneration and chemical hepatocarcinogenesis. Two other aspects of gene expression during compensatory and neoplastic growth of rat liver will also be explored: the existence of regulatory sequences and the relationships between patterns of gene expression in immature and neoplastic livers: 1) experiments have been designed to isolate and characterize nuclear RNA sequences detected in 12-16 h regenerating livers which may be nucleus-restricted regulatory sequences transcribed from reiterated genes; 2) the proportion of immature liver genes expressed in regenerating and neoplastic liver as well as in "oval cell" populations isolated from pre-neoplastic livers will be estimated directly with labeled, single-copy genomic DNA probes containing genes transcribed in fetal and neonatal livers.